(T0930-12-72) Preparation and In Vivo Evaluation of Sustained Release Docetaxel-Loaded Lipid Nanoparticles Using Hot Nanoemulsion-Based Technique

Purpose: To investigate the physicochemical properties, stability, anticancer effect and pharmacokinetics of docetaxel (DTX)-loaded lipid nanoparticles (NPs) prepared by hot nanoemulsion-based technique

Methods: DTX-loaded NPs were prepared by hot nanoemulsion-based technique using palmityl alcohol as a solid lipid and Tween 40/Span 40/Myrj S40 as surfactants mixture. DTX-loaded NPs were characterized in terms of particle size, polydispersity index, zeta potential, incorporation efficiency and TEM image. To test the stability of DTX-loaded NPs, particle size, polydispersity index, zeta potential and incorporation efficiency were monitored for 6 month at the 4°C and 25°C. In vitro release of DTX from NPs was studied in phosphate buffered saline (pH 7.4) using a dialysis bag method. Anticancer effect of DTX-loaded NPs was evaluated in mouse tumor models inoculated with MCF-7 human breast cancer cells. Pharmacokinetic studies were performed after intravenous administration of DTX-loaded NPs in rats at the dose of 10 mg/kg.

Results: DTX-loaded NPs had the particle size of 85.6 ± 1.9 nm and polydispersity index of 0.120 ± 0.027 with incorporation efficiency of 95.9 ± 2.6%. Particle size, polydispersity index, zeta potential and incorporation efficiency of DTX-loaded NPs were not significantly changed at 4°C for 6 months. In contrast, for the same period, significant changes in particle size, polydispersity index, zeta potential and incorporation efficiency were observed at 25°C. Commercial Taxotere^® formulation completely released DTX within 12h in phosphate buffered saline (pH 7.4). Meanwhile, DTX-loaded NPs slowly released 90% of DTX in 72 h. DTX-loaded NPs showed the enhanced anticancer effect in mouse tumor models. In pharmacokinetic study, AUC and half life of DTX-loaded NPs were found about 2.8- and 4.4-fold compared with Taxotere^® formulation.

Conclusion: The prolonged activity via the sustained release and improved bioavailability of DTX was achieved by DTX-loaded NPs.


A) Concentration-time profiles and (B) pharmacokinetic parameters of DTX in S.D. rats after intravenous administration of DTX-loaded NPs and Taxotere® at 5 mg/kg DTX dose.